The mechanisms of activation, proliferation, and differentiation of human B cells were studied. Particular attention was paid to the factors operative in the B cell cycle. A high molecular weight B cell growth factor (HMW-BCGF) was identified, isolated, characterized, and purified to homogeneity. Its specific binding to activated B cells was demonstrated. A monoclonal antibody directed against HMW-BCGF was produced which specifically inhibited the activity of the factor, specifically bound to the factor, and specifically absorbed out the factor from culture supernatants. The production of BCGF by normal B cells and malignant B cell lines was demonstrated suggesting an autocrine function for this factor. Interleukin-2 (IL-2) receptors were demonstrated on activated B cells and IL-2 was demonstrated to play a major role in the proliferation and differentiation of human B cells. Gamma-Interferon synergized with IL-2 in the induction of differentiation of B cells. The phenotypic expression of certain T cell clones were correlated with defined functional capabilities of the clone in the regulation of B cell function, particularly via production of B cell differentiation factor (BCDF). Human T cell clones and normal B cells were transformed with human T lymphotropic virus (HTLV-I) and used as a model system for the delineation of certain lymphoid cell functions such as the expression of IL-2 receptors and the response to IL-2. The pharmacologic modulation of the human immune response was studied particularly with regard to the effects of corticosteroids, cyclosporin A, transforming growth factor-Beta, and certain neuropeptides on certain distinct phases of the human B cell cycle.